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Vagal cholinergic denervation of the gastric mucosa in Long-COVID-19 (ijidonline.com)
104 points by thenerdhead 17 days ago
6 comments

8 people as the entire control group... yeah I'd say "may" is the operative word in the title. My takeaway from long covid is that it's probably as severe as the much more deadly pandemic of the Spanish Flu. Considering there's now a newfound interest in "long flu", I think a spotlight has now been placed on the impact of severe respiratory illness. Whether that illness be covid or one of the any other respiratory illnesses.
Yeah, twelve patients and eight in the control group isn't really a study.
is a small proof of concept study not a study anymore? gastric biopsies aren’t exactly easy to obtain at scale.
They are studies, and frankly, without something like this, doing things like the appropriate power calculations and risk assessments for larger studies would be hard to do.
I would consider things like these the equivalent of a test to see if a study is viable, not a study.

Sort of like, okay, if I have a hundred water balloons and I dropped fifty of those water balloons off the top of my house growing up, and fifty off the top of the Empire State building, would the latter always be that much worse? Just a few off the first and I can guess the outcome, and let's call that a control group, but the second, who knows... sure you might get lucky and knock one or two people out (or get a couple of good people showing results or seeming connections you want in a study) but you probably need more than a few to prove it isn't just a fluke. ;) Okay, messing around with the water balloons. Not with the study thing.

Funny that reactive arthritis has been around for decades but no one dares call it "long chlamydia" I guess it doesn't sell YouTube clicks as well.
wikipedia:

Reactive arthritis, previously known as Reiter's syndrome,[1] is a form of inflammatory arthritis[2] that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease.[3] By the time a person presents with symptoms, the "trigger" infection has often been cured or is in remission in chronic cases, thus making determination of the initial cause difficult.

The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis);[8] however, it also can happen after group A streptococcal infections.[9][10]

Usually they add “chronic” like chronic Lyme disease https://en.wikipedia.org/wiki/Chronic_Lyme_disease
severity is only one factor in developing long covid.

https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

hopefully we will get somewhere with these studies. The lack of solid research on a disease that affects millions (likely a good percentage undiagnosed) is really tough for patients - and myself really, as I've found i likely suffer from this.

Finding out about autonomic dysfunction and small fiber neuropathy as I researched my own fatigue and finding out I likely have this has been very challenging.

> as I researched my own fatigue and finding out I likely have this

Please don't do this. It's the medical equivalent of copy/pasting shit you don't understand from Stack Overflow.

Go see a doctor who has a degree and training.

As someone who has gone in to doctors for issues with fatigue, it’s incredibly draining (both emotionally and financially) to be batted around between a PCP and specialists that are unable to provide you with a diagnosis. I don’t blame anyone for just sitting down and trying to learn whatever they can by reading.

I agree with your general thrust of course, you’re much more likely to incorrectly diagnose yourself doing this than correctly, and walking around with a false belief is worse than walking around with uncertainty. But simply saying, “go see a doctor,” is rarely helpful. I’ve never heard of someone who tried to diagnose themselves without first presenting the issue to a physician.

If you feel tired the treatment is almost always symptomatic: stimulants and wakefulness promoters.

If you sleep over 11 hrs per 24 hours: that’s pathological and they will be prescribed.

Fall asleep faster than X minutes? Same diagnosis, same meds.

Have apnea and yet still fatigued/sleepy after CPAP/surgery? Same meds.

Fulfill criteria for ADHD? Same meds.

Fatigue after TBI? Same meds.

Fatigue with MS? Same meds.

The root cause may or may not be eventually found, but there is no reason to get diagnosed with whatever is most useful to begin at least supporting treatment.

Autonomic neurologists are the relevant specialists. I invite you to look for one in your local area and see how rare they are. The last I checked, the Seattle metro area (and in fact the whole state of Washington) had precisely one board-certified autonomic neurologist. Diagnostic delay is, unsurprisingly, around six years. Combine that with the fact that all the equipment you need to do a basic POTS test is a pulse oximeter and a blood pressure cuff, and yeah, you're going to have people self-diagnosing, for good reason.
I did see a doctor.
Oh sorry, I didn’t mean to imply you didn’t. If you were lucky enough to get a doctor to diagnose you before you figured it out yourself, congrats. That should be more common than it is. There are way too many doctors out there brushing off obvious signs of small fiber neuropathy.
If there's no test for it, then what is the doctor going to do for something as nebulous as long covid?
Plenty of tests. Autonomic medicine is not nebulous, more often than not what’s happening is some homeostasis failure/some peripheral nerve thing/brain damage. At the very minimum.

Widespread issues all over the body without readily obvious organ damage is nearly always nerves/brain.

99% of physicians wouldn’t know what to do with specialized test results anyway, even if they’d know what/how to order in the first place. Internists don’t know how to read PET scans, radiologists don’t know anything about homeostasis. general radiology cant even read head&neck scans, you want a specialized radiologist for that. geneticists don’t have the slightest idea about how to read nerve studies, which is actually a completely separate certification, not even every neurologist has it or does them.

Medicine is the game of super-specialization.

And nobody wants to bother to try to piece it all together for you. Very few MDs are actually able to, in the first place.

Ideally, you have a very broadly competent internist to figure out what direction to even start digging at, and then find the sub specialist who has the expertise AND interest in that area.

eg NIH’s section on neuro cardiology recently closed because this one dude who was REALLY into simply was too old, couldnt find a replacement or build a bigger lab that could sustain itself and retired.

At times you need a specialist trained and practicing in two different specialties: eg ENT + neuro, for example. Those can be hard to find. Neuro cardio more common especially now.

There are tests for it. SFN biopsy, tilt table, ETT.
I did see a doctor. I’m mid diagnosis / testing.
It's probably more profitable to treat symptoms.
Hard to treat symptoms with immunological conditions. I mean, there are vitamins and supplements, but noone is gonna generally hand out economy-sized bottles of controlled substances for exhaustion, etc.

These sorts of conditions are systemic, and the causes and ways of dealing with the accompanying syndromes are probably always going to be different from individual to individual (well, likely the exact physiological causes anyway).

So far all the trials attempting to do so have failed. Its not that people aren't trying this, it just doesn't work for most of the symptoms.
It's true, this is why there are so many government agencies focused on healthcare. The medical field lacks a healthy profit motive. Healthcare CEOs use their fiduciary responsibilities as an excuse and say they'll get sued if they don't exploit situations.

There was a SARS vaccine as far as back 2016 which could have changed everything but was ignored. Pharmaceutical execs told them they were, "waiting to see if it comes back yearly" first

Wow mucosal innervation was around half in long covid patients - that's super worrying and would have nasty symptoms in practice.

The findings also support the hypothesis that SARS-CoV-2 may cause structural nerve damage, which is perhaps the even bigger worry. :(

What kind of symptoms? I have insane stomach issues since early 2021 that only this year started to largely subside.
Any Long Covid patient can tell you its damaged their nerves, they can feel it. Nerve pain all over and various weird zaps and shakes etc, the nervous system is clearly damaged/being damaged across the entire body.
This is I believe one of the markers for small fiber neuropathy which is now increasingly being found in association with long covid and related syndromes.
All the B12 and gabapentin in the world won't reverse the damage, but at least there's hope.
i noticed a thing with headlines like these: "x may cause y". Whenever it's "may" or "might", it's almost always meaningless
There has been a shift - an understandable one, and one I by and large support (absent some edge cases) - to move away from causal language for observational studies.
small study yes, meaningless no
Only the Sith deal in absolutes.
Is there a test for long covid?
Think of AIDS before the immune system dysfunction was found. That's where we are with Long Covid. One cause, a myriad of apparently unrelated effects--that's not how biology tends to work. Rather, there's something deeper we haven't found. And we certainly can't test for what we haven't found.
This is nothing like AIDS.
I am not in any way implying the diseases are related!

I'm saying that it's "like" AIDS in that we are seeing only the top layer, we don't understand what connects them. With AIDS we in time found a common failure in the immune system that by itself didn't produce symptoms, just enabled other failures. And then we found the virus that causes that immune failure.

With Long Covid we have not yet recognized whatever failure they have in common.

And look at how society reacted to AIDS back then. We are doing a lot of the same things with Long Covid.

Yes it is. It's a virus that affects humans. There are. million differences and a million more similarities, saying it's nothing like AIDS without any qualification is just making noise.
There's no such thing as "long COVID" specifically. Any serious viral infection has the potential to cause sequalae in susceptible patients for reasons that are still not well understood. Some of those are detectible in lab tests to an extent but there's no single clear diagnostic test.
It's long as in persistent viral colonization, often in immune privileged areas where the virus can hide from the immune system.

One theory is that the immune system doesn't always produce a strong enough antibody response to flush the virus from all these areas but the truth is that's likely only a subset of total cases.

they are pretty well understood now with growing evidence of viral persistence in the gut and immune cells, and immune dysfunction causing autoantibodies.

they are also distinct from other conditions like ME/CFS or other sequelae although they may share overlapping symptoms. A lot of research is going into different PAIS post acute infection syndromes

Isnt CFS notoriously post-viral?
evidence says yes, but bacteria and other antigens are being studied. ME/CFS shows antigen persistence like long covid has clearly shown.

https://www.nature.com/articles/s41467-024-45107-3

Interesting, then I guess the obvious next question is … is there a test for being a susceptible patient? We’ve been talking about long COVID for years now. Surely there’s some commonalities amongst the people who suffer from it.
not quite. A grab bag of biomarkers being validated in research labs across the USA though
Nothing you can order from your doctor yet but plenty of abnormal findings in almost every aspect of the body. As far as I know none of the findings yet is found in every sufferer, a combination can often get to ~95% but its very heterogenous and that has made it very hard to come up with a single test.
Wouldn’t this be completely expected though?

A sizable percentage of autoimmune cases of well accepted autoimmune diseases (rheumatoid arthritis, celiac, etc etc etc ) are completely seronegative despite glaringly obvious clinical signs: eg peeing skin, deformed joints etc etc - all blood work perfectly normal. Happens all the time.

Why would we expect anything different here?

Firstly the term 'long' is not good. Better is post-COVID syndrom, because the virus has been eliminated and not staying for long but the situation remains post infection.

Secondly, the majority of burden is caused by CNS/brain dysfunction, especially a form of neurotransmitter depletion, and not due to peripheral autonomous imbalance. And the former is a much more difficult therapeutic target: in my experience incurable for ever but also quite more rare that it is shown in the media.